Follow-up computed tomography and unexpected hemostasis in non-operative management of pediatric blunt liver and spleen injury.

PURPOSE: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). METHODS: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. RESULTS: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). CONCLUSION: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

INTRODUCTION: Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. METHODS: A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. RESULTS: A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (ß: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (ß: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. CONCLUSIONS: In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Retrospective analysis of the effects of hypocalcemia in severely injured trauma patients.

BACKGROUND: It has been suggested that the Lethal Triad be modified to include hypocalcemia, coined as the Lethal Diamond. Hypocalcemia in trauma has been attributed to multiple mechanisms, but new evidence suggests that traumatic injury may result in the development of hypoCa independent of blood transfusion. We hypothesize that hypocalcemia is associated with increased blood product requirements and mortality. METHODS: A retrospective study of 1,981 severely injured adult trauma patients from 2016 to 2019. Ionized calcium (iCa) levels were obtained on arrival and subjects were categorized by a threshold iCa level of 1.00 mmol/L and compared. Univariable and multivariable logistic regression analysis was performed. RESULTS: The hypocalcemia (iCa <1.00 mmol/L) group had increased rate of overall (p = 0.001), 4-hr (p = 0.007), and 24-hr (p = 0.003) mortality. There was no difference in prehospital transfusion volume between groups (p = 0.25). Hypocalcemia was associated with increased blood product requirements at 4 h (p <0.001), 24 h (p <0.001), and overall hospital length of stay (p <0.001). Logistic regression analysis showed increased odds of 4-hour mortality (OR 0.077 [95 % CI 0.011, 0.523], p = 0.009) and 24-hour mortality (OR 0.121 [95 % CI 0.019, 0.758], p = 0.024) for every mmol/L increase in iCa. CONCLUSIONS: This study shows the association of hypoCa and traumatic injury. Severe hypoCa was associated with increased odds of early and overall mortality and increased blood product requirements. These results support the need for future prospective trials assessing the role of hypocalcemia in trauma.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial.

Background: Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. Methods: We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. Results: NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (ß=-27.6, 95% CI (-51.3 to -3.9), p=0.02). Conclusions: Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. Level of evidence: Level II.

Immediate Angiography and Decreased In-Hospital Mortality of Adult Trauma Patients: A Nationwide Study.

PURPOSE: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. MATERIALS AND METHODS: We conducted a retrospective cohort study using a nationwide trauma databank (2019-2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. RESULTS: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31-0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22-0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26-0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. CONCLUSION: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. LEVEL OF EVIDENCE: Level 3b, non randomized controlled cohort/follow up study.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Emergency preparedness for mass casualty events: South Texas commentary on the development of a statewide emergency response system.

Mass casualty incidents (MCIs) are on the rise in the USA, and hemorrhage is the leading cause of preventable death in trauma. The need for rapid access to life-saving blood and blood products is essential for preventing death due to hemorrhage. It is well established that most major cities in the USA are underprepared to meet blood transfusion requirements in the event of an MCI. The South Texas Whole Blood Consortium sought to rectify this and vowed to be prepared to provide low-titer type O-positive whole blood (LTOWB) and blood components to the people who need it, where and when they need it. This system was able to transport 25 units of LTOWB and packed red blood cells almost 100 miles away to Uvalde Memorial Hospital within just 67 minutes after notification of an active shooter. The regional consortium has created a pool of dedicated LTOWB donors affectionately called Heroes in Arms who can be called on to instantly augment locoregional blood supply. Previously pregnant women have historically been excluded from donating plasma and LTOWB due to the increased rates of human leukocyte antigen (HLA) antibody (Ab) positivity, which is associated with transfusion-related acute lung injury. However, the South Texas Blood and Tissue Center in San Antonio had a large number of qualified, previously pregnant females desire to join the Heroes in Arms program prompting them to assess the feasibility of providing HLA Ab testing for this demographic and the results were promising. This is the first report of previously pregnant women being included in the pool for donation of LTOWB.

Walking blood bank: a plan to ensure self-sufficiency in an era of blood shortage.

Mass casualty incidents and massive transfusion requirements continue to plague the USA with hemorrhage remaining the number one cause of death in trauma. The unfortunate reality of numerous mass shootings in Southwest Texas has led to the need for a way in which to provide blood during these events as rapidly as it is required. Multiple agencies within the Southwest Texas system have united to help provide this life-saving blood to people when they need it most. This effort began with the development of a system for safe, efficient, and now widespread use of whole blood in the region. After demonstrating the success of delivering large quantities of blood during the Uvalde shooting, we have begun to develop a walking blood bank that is similar to what the miliary uses on the battlefield. The concept behind this initiative is to have a cohort of whole blood donors who are preselected to join the program which is now dubbed 'Heroes in Arms'. These donors will be called upon to donate whole blood during a massive transfusion event. Their blood will be rapidly screened prior to transfusion to the patient. This blood will still undergo the normal rigorous testing and, should any potentially transmissible diseases by discovered post-transfusion, the individual who received that product will be treated accordingly. Given the low rate of transmissible disease among this preselected population, combined with rapid screening prior to transfusion, the risk of a person receiving a transmissible disease is insignificant in comparison to the benefit of having blood to transfuse during hemorrhage. This model is a promising collaborative effort to provide in a timely and sufficient blood product in cases of major need which will consequently minimize the number of traumatically injured civilian patients who die from hemorrhage.

EVIDENCE FOR BENEFICIAL USE OF THE COMPENSATORY RESERVE MEASUREMENT IN GUIDING INTRAOPERATIVE RESUSCITATION: A PROSPECTIVE COHORT STUDY OF ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS.

ABSTRACT: Introduction: The compensatory reserve measurement (CRM) is a continuous noninvasive monitoring technology that provides an assessment of the integrated capacity of all physiological mechanisms associated with responses to a hypovolemic stressor such as hemorrhagic shock. No prior studies have analyzed its use for intraoperative resuscitation guidance. Methods: A prospective observational study was conducted of 23 patients undergoing orthotopic liver transplant. Chart review was performed to identify timing of various intraoperative events. Data were compared based on predefined thresholds for existence of hemorrhagic shock: CRM lower than 40%, systolic blood pressure (SBP) lower than 90 mm Hg (SBP90), and heart rate (HR) higher than 100 beats per minute (HR100). Regression analysis was performed for predicting resuscitation events, and nonlinear eXtreme Gradient Boosting (XGBoost) models were used to compare CRM with standard vital sign measures. Results: Events where CRM dropped lower than 40% were 2.25 times more likely to lead to an intervention, whereas HR100 and SBP90 were not associated with intraoperative interventions. XGBoost prediction models showed superior discriminatory capacity of CRM alone compared with the model with SBP and HR and no difference when all three were combined (CRM-HR-SBP). All XGBoost models outperformed equivalent linear regression models. Conclusion: These results demonstrate that CRM can provide an adjunctive clinical tool that can augment early and accurate of hemodynamic compromise and promote goal-directed resuscitation in the perioperative setting.

Intraoperative Use of Compensatory Reserve Measurement in Orthotopic Liver Transplant: Improved Sensitivity for the Prediction of Hypovolemic Events.

INTRODUCTION: The compensatory reserve measurement (CRM) is a continuous non-invasive monitoring technology that measures the summation of all physiological mechanisms involved in the compensatory response to central hypovolemia. The CRM is displayed on a 0% to 100% scale. The objective of this study is to characterize the use of CRM in the operative setting and determine its ability to predict hypovolemic events compared to standard vital signs. Orthotopic liver transplant was used as the reference procedure because of the predictable occurrence of significant hemodynamic shifts. METHODS: A prospective observational cohort study was conducted on 22 consecutive patients undergoing orthotopic liver transplant. The subjects were monitored in accordance with the standard of care. The CRM data were collected concurrently with intraoperative staff blinded to the outputs. The data were stored on secure devices on encrypted files. Based on prior literature, subgroup analysis was performed for high-tolerance (good compensators) and low-tolerance (poor compensators) groups, which was based on a shock index threshold of 0.9. Threshold events were defined as follows: CRM below 60% (CRM60), systolic blood pressure (SBP) below 90 mmHg (SBP90), and heart rate (HR) above 100 beats per minute (HR100). RESULTS: Complete data were captured in 22 subjects as a result of device malfunction or procedure cancellation. Sensitivity analysis was performed for the detection of hypovolemia at the time of the event. CRM60 was the most sensitive (62.6%) when compared to other threshold measures such as SBP90 (30.6%), HR100 (23.1%), elevated lactate (54.6%), and a drop in hemoglobin (41.7%). The number of patients meeting the CRM60 threshold at the time of the first transfusion (TFX) was higher when compared to SBP90 and HR100 in the overall group (P = .001 and P < .001, respectively) and both the high-tolerance (P = .002 and P = .001, respectively) and low-tolerance groups (P = .016 and P = .001, respectively). Similar results supporting the higher sensitivity of CRM were observed when comparing the number of patients below the threshold at the time of the first vasopressor administration. Start time was standardized so that the time-to-threshold signals for hemodynamic and laboratory parameters could be compared. The median time-to-CRM signal detection before the TFX event was -15.0 minutes (i.e., 15 minutes before TFX). There was no difference when compared to the SBP threshold (median time -5.0 minutes, P = .64) but was significantly sooner when compared to HR (P = .006), lactate (P = .002), and hemoglobin (P < .001). CONCLUSIONS: At the time of the first TFX, the CRM had a higher rate of detection of a hypovolemic event compared to SBP and HR, indicating a higher sensitivity for the detection of the first hypovolemic event. When combined with all hypovolemic events, sensitivity analysis showed that CRM60 provides the earlier predictive capability. Given that SBP is the clinical standard of care for the initiation of TFX, the finding that median time to event detection was statistically similar between CRM60 and SBP90 was not unexpected. When compared to other measures of hypovolemia, the CRM consistently showed earlier detection of hypovolemic events. Although this study had a small sample size, it produced significant results and can serve as a proof of concept for future large-scale studies.

TITAN CSR: a new self-retaining retractor for abdominal surgery.

Background: Self-retaining retractors provide hands-free exposure and allow surgeons to use their hands to perform surgery rather than manually retract tissues. Non-table-mounted retractors offer rapid assembly, but they have been traditionally limited in their ability to provide adequate exposure of the abdomen. Table-mounted retractors provide excellent exposure, but their cumbersome and time-intensive assembly often precludes their use in emergency settings. The TITAN CSR surgical retractor is a novel, lightweight, expandable, and modular system which offers the benefits of both designs by providing rapid assembly and effective abdominal exposure without a table attachment. We describe our experience with this new retractor system. Methods: Retrospective case series of selected trauma and emergency surgery laparotomies at an urban academic level 1 trauma center using the TITAN CSR surgical retractor during a 1-year period. Results: The TITAN CSR surgical retractor was used to provide exposure for trauma and emergency surgery laparotomies in both adult and pediatric patients in 89 cases from July 2021 to July 2022. Without requiring a table attachment, the TITAN CSR retractor provided hands-free surgical exposure during a variety of procedures including traumatic hysterectomy, gastrorrhaphy, enterorrhaphies and colectomy. With the added utility of attaching Bookwalter-compatible retractor blades, it provided effective exposure of retroperitoneal structures. These structures included the inferior vena cava, left femoral vessels, and duodenum. All laparotomies presented were successfully completed without setting up a post or a connection to the surgical table. Discussion: The TITAN CSR surgical retractor was successfully used in a number of difficult trauma and emergency surgery laparotomies, providing effective intra-abdominal and retroperitoneal exposure without necessitating an attachment to the surgical table. This retractor has the potential to replace current retractor systems in abdominal surgery, providing the benefits of table-mounted and non-table-mounted designs while removing their various disadvantages.

Access to trauma center care: A statewide system-based approach.

BACKGROUND: Timely access to specialized trauma care is a vital element in patient outcome after severe and critical injury requiring the skills of trauma teams in levels I and II trauma centers to avoid preventable mortality. We used system-based models to estimate timely access to care. METHODS: Trauma system models consisted of ground emergency medical services, helicopter emergency medical services, and designated levels I to V trauma centers were constructed for five states. These models incorporated geographic information systems along with traffic data and census block group data to estimate population access to trauma care within the "golden hour." Trauma systems were further analyzed to identify the optimal location for an additional level I or II trauma center that would provide the greatest increase in access. RESULTS: The population of the states studied totaled 23 million people, of which 20 million (87%) had access to a level I or II trauma center within 60 minutes. Statewide-specific access ranged from 60% to 100%. Including levels III to V trauma centers, access within 60 minutes increased to 22 million (96%), ranging from 95% to 100%. The addition of a levels I and II trauma center in an optimized location in each state would provide timely access to a higher trauma capability for an additional 1.1 million, increasing total access to approximately 21.1 million people (92%). CONCLUSION: This analysis demonstrates that nearly universal access to trauma care is present in these states when including levels I to V trauma centers. However, concerning gaps remain in timely access to levels I and II trauma centers. This study provides an approach to determine more robust statewide estimates of access to care. It highlights the need for a national trauma system, one in which all components of state-managed trauma systems are assembled in a national data set to accurately identify gaps in care. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Burden of unintentional pediatric firearm injury: An examination of the Nationwide Readmission Database.

BACKGROUND: Significant increases in firearm-related mortality in the US pediatric population drive an urgent need to study these injuries to drive prevention policies. The purpose of this study was (1) to characterize those with and without readmissions, (2) to identify risk factors for 90-day unplanned readmission, and (3) to examine reasons for hospital readmission. METHODS: The 2016-2019 Nationwide Readmission Database of the Healthcare Cost and Utilization Project was used to identify hospital admissions with unintentional firearm injury in patients younger than 18 years. Ninety-day unplanned readmission characteristics were assessed and detailed. Multivariable regression analysis was used to assess factors associated with unplanned 90-day readmission. RESULTS: Over 4 years, 1,264 unintentional firearm injury admissions resulted in 113 subsequent readmissions (8.9%). There were no significant differences in age or payor, but more women (14.7% vs. 23%) and older children (13-17 years [80.5%]) had readmissions. The mortality rate during primary hospitalization was 5.1%. Survivors of initial firearm injury were more frequently readmitted if they had a mental health diagnosis (22.1% vs. 13.8%; p = 0.017). Readmission diagnosis included complications (15%), mental health or drug/alcohol (9.7%), trauma (33.6%), a combination of the prior three (28.3%), and chronic disease (13.3%). More than a third (38.9%) of the trauma readmissions were for new traumatic injury. Female children, those with longer lengths of stay, and those with more severe injuries were more likely to have unplanned 90-day readmissions. Mental health and drug/alcohol abuse diagnoses were not an independent predictor for readmission. CONCLUSION: This study provides insight into the characteristics of and risk factors for unplanned readmission in the pediatric unintentional firearm injury population. In addition to using prevention strategies, the utilization of trauma-informed care must be integrated into all aspects of care for this population to help minimize the long-term psychological impact of surviving firearm injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.

BACKGROUND: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). CONCLUSION: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Risk factors for massive transfusion in obstetrical hemorrhage and consideration of a whole blood program.

BACKGROUND: Postpartum hemorrhage (PPH) is one of the leading causes of obstetric complications. The goal of this study was to identify risk factors for obstetric (OB) massive transfusion (MT) and determine the feasibility of developing a low-titer group O RhD-positive whole blood (LTO + WB) protocol for OB hemorrhage. STUDY DESIGN AND METHODS: A retrospective study of OB patients who received transfusion within 24 h. MT patients were those who received >3 U of pRBC within 1 h or > 10 U in 24 h. Patient demographics, OB history, comorbidities, blood type, antibody status, and known risk factors for PPH and maternal-fetal outcomes were compared. Logistic regression was used for univariate and multivariate analyses. RESULTS: Of the 610 transfused OB patients, 12.0% (n = 73) required MT. Groups were well matched for body mass index (BMI), maternal comorbidities, and history of spontaneous vaginal deliveries. The incidence of the previous cesarean section was higher in the MT group. Exactly 93.9% of patients were RhD-positive and 3.77% of all patients possessed an antibody on pretransfusion testing. Patients with MT had a longer length of stay (LOS), higher rate of intensive care unit (ICU) admission, fetal death, and hysterectomy. Multivariate analysis found age >35, PPH, placenta percreta, accreta, and increta to be significant (p < .05) risk factors for MT. DISCUSSION: Patients over 35 years and those with abnormal placentation are at increased risk of requiring MT. With a time to delivery of 2 days, potential MT patients can be identified early, and with a 94% rate of RhD-positive+, they are eligible to receive low-titer O whole blood (LTOWB) providing hemostatic resuscitation with reduced donor exposure.

The impact of prehospital whole blood on hemorrhaging trauma patients: A multi-center retrospective study.

BACKGROUND: Whole blood (WB) use has become increasingly common in trauma centers across the United States for both in-hospital and prehospital resuscitation. We hypothesize that prehospital WB (pWB) use in trauma patients with suspected hemorrhage will result in improved hemodynamic status and reduced in-hospital blood product requirements. METHODS: The institutional trauma registries of two academic level I trauma centers were queried for all patients from 2015-2019 who underwent transfusion upon arrival to the trauma bay. Patients who were dead on arrival or had isolated head injuries were excluded. Demographics, injury and shock characteristics, transfusion requirements, including massive transfusion protocol (MTP) (>10 U in 24 hours) and rapid transfusion (CAT3+) and outcomes were compared between pWB and non-pWB patients. Significantly different demographic, injury characteristics and pWB were included in univariate followed by stepwise logistic regression analysis to determine the relationship with shock index (SI). Our primary objective was to determine the relationship between pWB and improved hemodynamics or reduction in blood product utilization. RESULTS: A total of 171 pWB and 1391 non-pWB patients met inclusion criteria. Prehospital WB patients had a lower median Injury Severity Score (17 vs. 21, p < 0.001) but higher prehospital SI showing greater physiologic disarray. Prehospital WB was associated with improvement in SI (-0.04 vs. 0.05, p = 0.002). Mortality and (LOS) were similar. Prehospital WB patients received fewer packed red blood cells, fresh frozen plasma, and platelets units across their LOS but total units and volumes were similar. Prehospital WB patients had fewer MTPs (22.6% vs. 32.4%, p = 0.01) despite a similar requirement of CAT3+ transfusion upon arrival. CONCLUSION: Prehospital WB administration is associated with a greater improvement in SI and a reduction in MTP. This study is limited by its lack of power to detect a mortality difference. Prospective randomized controlled trials will be required to determine the true impact of pWB on trauma patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Transfusion-related cost comparison of trauma patients receiving whole blood versus component therapy.

INTRODUCTION: With the emergence of whole blood (WB) in trauma resuscitation, cost-related comparisons are of significant importance to providers, blood banks, and hospital systems throughout the country. The objective of this study was to determine if there is a transfusion-related cost difference between trauma patients who received low titer O+ whole blood (LTO+WB) and component therapy (CT). METHODS: A retrospective review of adult and pediatric trauma patients who received either LTO+WB or CT from time of injury to within 4 hours of arrival was performed. Annual mean cost per unit of blood product was obtained from the regional blood bank supplier. Pediatric and adult patients were analyzed separately and were compared on a cost per patient (cost/patient) and cost per patient per milliliter (cost/patient/mL) basis. Subgroup analysis was performed on severely injured adult patients (Injury Severity Score, >15) and patients who underwent massive transfusion. RESULTS: Prehospital LTO+WB transfusion began at this institution in January 2018. After the initiation of the WB transfusion, the mean annual cost decreased 17.3% for all blood products, and the average net difference in cost related to component blood products and LTO+WB was more than $927,000. In adults, LTO+WB was associated with a significantly lower cost/patient and cost/patient/mL compared with CT at 4 hours ( p < 0.001), at 24 hours ( p < 0.001), and overall ( p < 0.001). In the severely injured subgroup (Injury Severity Score, >15), WB was associated with a lower cost/patient and cost/patient/mL at 4 hours ( p < 0.001), 24 hours ( p < 0.001), and overall ( p < 0.001), with no difference in the prehospital setting. Similar findings were true in patients meeting massive transfusion criteria, although differences in injury severity may account for this finding. CONCLUSION: With increased use of LTO+WB for resuscitation, cost comparison is of significant importance to all stakeholders. Low titer O+ WB was associated with reduced cost in severely injured patients. Ongoing analyses may improve resource utilization and benefit overall healthcare cost. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The effects of hypocalcemia in severely injured pediatric trauma patients.

INTRODUCTION: The role of calcium is ubiquitous in human physiology. Emerging evidence suggests that the lethal triad be revised to include hypocalcemia (hypoCa) and thus be known as the lethal diamond . There are data showing that traumatic injury may result in hypoCa independent from the mechanism of calcium chelation by citrate-based blood preservatives. Minimal literature exists analyzing the role of hypoCa in pediatric trauma patients. We hypothesize that there is an independent association of hypoCa with increased blood product requirements and mortality. METHODS: A retrospective cohort study of severely injured pediatric trauma patients was conducted. Trauma registry data were collected from January 2016 to August 2021. Ionized calcium (iCa) levels were obtained from arrival blood draws. Subjects were categorized into two groups by a threshold iCa level of 1.00 mmol/L and compared. Shock Index Pediatric Adjusted scores were used to adjust for age-specific differences in vital signs. RESULTS: A total of 142 patients were compared, of which 46.5% were hypocalcemic (iCa <1.00 mmol/L). Patients were well matched in terms of demographics and injury severity. The hypocalcemic group had lower systolic blood pressure and a higher percentage of Shock Index Pediatric Adjusted-positive patients. Weight-adjusted transfusion volumes were significantly higher in the hypocalcemic group at both the 4-hour and 24-hour time points without a difference in prehospital transfusion requirements. There was no observed difference in early or in-hospital mortality. CONCLUSION: This study contributes to the body of literature regarding the association between hypoCa and traumatic injury in the pediatric population. Hypocalcemia was associated with increased blood product requirements without a difference in prehospital transfusion requirements, suggesting a possible independent association. Further prospective studies are needed to better understand this relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Time to early resuscitative intervention association with mortality in trauma patients at risk for hemorrhage.

BACKGROUND: Hemorrhage is the leading cause of preventable death after injury. Others have shown that delays in massive transfusion cooler arrival increase mortality, while prehospital blood product resuscitation can reduce mortality. Our objective was to evaluate if time to resuscitation initiation impacts mortality. METHODS: We combined data from the Prehospital Air Medical Plasma (PAMPer) trial in which patients received prehospital plasma or standard care and the Study of Tranexamic Acid during Air and ground Medical Prehospital transport (STAAMP) trial in which patients received prehospital tranexamic acid or placebo. We evaluated the time to early resuscitative intervention (TERI) as time from emergency medical services arrival to packed red blood cells, plasma, or tranexamic acid initiation in the field or within 90 minutes of trauma center arrival. For patients not receiving an early resuscitative intervention, the TERI was calculated based on trauma center arrival as earliest opportunity to receive a resuscitative intervention and were propensity matched to those that did to account for selection bias. Mixed-effects logistic regression assessed the association of 30-day and 24-hour mortality with TERI adjusting for confounders. We also evaluated a subgroup of only patients receiving an early resuscitative intervention as defined above. RESULTS: Among the 1,504 propensity-matched patients, every 1-minute delay in TERI was associated with 2% increase in the odds of 30-day mortality (adjusted odds ratio [aOR], 1.020; 95% confidence interval [CI], 1.006-1.033; p < 0.01) and 1.5% increase in odds of 24-hour mortality (aOR, 1.015; 95% CI, 1.001-1.029; p = 0.03). Among the 799 patients receiving an early resuscitative intervention, every 1-minute increase in TERI was associated with a 2% increase in the odds of 30-day mortality (aOR, 1.021; 95% CI, 1.005-1.038; p = 0.01) and 24-hour mortality (aOR, 1.023; 95% CI, 1.005-1.042; p = 0.01). CONCLUSION: Time to early resuscitative intervention is associated with morality in trauma patients with hemorrhagic shock. Bleeding patients need resuscitation initiated early, whether at the trauma center in systems with short prehospital times or in the field when prehospital time is prolonged. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Evaluation of critical care burden following traumatic injury from two randomized controlled trials.

Trauma resuscitation practices have continued to improve with new advances targeting prehospital interventions. The critical care burden associated with severely injured patients at risk of hemorrhage has been poorly characterized. We aim to describe the individual and additive effects of multiorgan failure (MOF) and nosocomial infection (NI) on delayed mortality and resource utilization. A secondary analysis of harmonized data from two large prehospital randomized controlled trials (Prehospital Air Medical Plasma (PAMPer) Trial and Study of Tranexamic Acid during Air and Ground Medical Prehospital Transport (STAAMP) Trial) was conducted. Only those patients who survived beyond the first 24 hours post-injury and spent at least one day in the ICU were included. Patients were stratified by development of MOF only, NI only, both, or neither and diagnosis of early (≤ 3 days) versus late MOF (> 3 days). Risk factors of NI and MOF, time course of these ICU complications, associated mortality, and hospital resource utilization were evaluated. Of the 869 patients who were enrolled in PAMPer and STAAMP and who met study criteria, 27.4% developed MOF only (n = 238), 10.9% developed NI only (n = 95), and 15.3% were diagnosed with both MOF and NI (n = 133). Patients developing NI and/or MOF compared to those who had an uncomplicated ICU course had greater injury severity, lower GCS, and greater shock indexes. Early MOF occurred in isolation, while late MOF more often followed NI. MOF was associated with 65% higher independent risk of 30-day mortality when adjusting for cofounders (OR 1.65; 95% CI 1.04-2.6; p = 0.03), however NI did not significantly affect odds of mortality. NI was individually associated with longer mechanical ventilation, ICU stay, hospital stay, and rehabilitation requirements, and the addition of MOF further increased the burden of inpatient and post-discharge care. MOF and NI remain common complications for those who survive traumatic injury. MOF is a robust independent predictor of mortality following injury in this cohort, and NI is associated with higher resource utilization. Timing of these ICU complications may reveal differences in pathophysiology and offer targets for continued advancements in treatment.